Bio-impedance spectroscopy added to a fluid management protocol does not improve preservation of residual kidney function in incident hemodialysis patients in a randomized controlled trial.

Avoiding excessive dialysis-associated volume depletion may help preserve residual kidney function (RKF). To establish whether knowledge of the estimated normally hydrated weight from bioimpedance measurements (BI-NHW) when setting the post-hemodialysis target weight (TW) might mitigate rate of loss of RKF, we undertook an open label, randomized controlled trial in incident patients receiving HD, with clinicians and patients blinded to bioimpedance readings in controls. A total of 439 patients with over 500 ml urine/day or residual GFR exceeding 3 ml/min/1.73m2 were recruited from 34 United Kingdom centers and randomized 1:1, stratified by center. Fluid assessments were made for up to 24 months using a standardized proforma in both groups, supplemented by availability of BI-NHW in the intervention group. Primary outcome was time to anuria, analyzed using competing-risk survival models adjusted for baseline characteristics, by intention to treat. Secondary outcomes included rate of RKF decline (mean urea and creatinine clearance), blood pressure and patient-reported outcomes. There were no group differences in cause-specific hazard rates of anuria (0.751; 95% confidence interval (0.459, 1.229)) or sub-distribution hazard rates (0.742 (0.453, 1.215)). RKF decline was markedly slower than anticipated, pooled linear rates in year 1: -0.178 (-0.196, -0.159)), year 2: -0.061 (-0.086, -0.036)) ml/min/1.73m2/month. Blood pressure and patient-reported outcomes did not differ by group. The mean difference agreement between TW and BI-NHW was similar for both groups, Bioimpedance: -0.04 kg; Control: -0.25 kg. Thus, use of a standardized clinical protocol for fluid assessment when setting TW is associated with excellent preservation of RKF. Hence, bioimpedance measurements are not necessary to achieve this.

Buprenorphine Prescribing and Dosing Limits: Evidence and Policy Goals.

The opioid misuse epidemic is a serious public health crisis. Opioid-involved deaths continue to rise and the potency of illicitly manufactured synthetic opioids has increased, creating challenges for the healthcare system to provide multifaceted specialized care. Elements of the regulation around buprenorphine, 1 of 3 drugs approved to treat opioid use disorder (OUD), constrain treatment options for patients and providers alike. Updates to this regulatory framework, particularly around dosing and access to care, would enable providers to better treat the changing landscape of opioid misuse. Specific actions to this end are to: (1) Increase buprenorphine dosing flexibility based on FDA labeling which drives payor policies; (2) Restrict local government and institutional impositions of arbitrary access and dosing limits for buprenorphine; and (3) Liberalize buprenorphine initiation and maintenance via telemedicine for OUD.

History of endoscopic treatment of vesicoureteral reflux.

Since its first clinical application in 1984, the endoscopic subureteral injection of bulking agents has become an alternative to long-term antibiotic prophylaxis and open surgical intervention in the treatment of VUR in children. The 15 min day care endoscopic procedure has gained worldwide popularity in the management of VUR in children. Over the years, multiple studies have demonstrated safety and long-term efficacy of this minimally invasive outpatient procedure. Nowadays almost 90% of the surgical treatment of VUR in Sweden is done by endoscopic procedure. In the current article, our aim was to review how the endoscopic treatment of VUR developed.

Paediatric urology in Sub-Saharan Africa: challenges and opportunities.

The need for paediatric urological care in low- and middle-income countries in sub-Saharan Africa (SSA) is enormous due to a burgeoning paediatric-aged population and a disproportionate burden of congenital malformations. There are formidable challenges in the provision of a skilled workforce and appropriate infrastructure, resulting in a huge unmet need with consequent effects on the long-term health and prosperity of the population. Constraints of funding, geography, culture, surgical and anaesthetic skills, and instrumentation means that many conditions present late and with complications that could have been avoided by an earlier attendance. It also means that the management of congenital malformations, e.g., bladder exstrophy and congenital obstructive posterior urethral membrane, differ substantially from that seen in the developed world, with the outlook for children with renal failure being particularly bleak. Collaborations between paediatric urologists from high- and low-income countries are beginning to help with the development of a surgical infrastructure customised to paediatric care, and with the training of specific paediatric urological knowledge and skills. These collaborations, whilst welcome, still require substantial expansion to achieve more equitable access to appropriate paediatric urological care for children in SSA. Future efforts have to focus on the creation of sustainable and equal partnerships between urologists from low- and high-income healthcare environments, with an emphasis on providing sustainable management, appropriate to local need and available resources. The provision of shared learning, utilising the benefits of global digital communication, will improve mutual understanding of needs in a resource-poor environment and the involvement of trainees from both income settings can help perpetuate long-term collaborations.

Examining the effect of Libet clock stimulus parameters on temporal binding.

Temporal binding refers to the subjective temporal compression between actions and their outcomes. It is widely used as an implicit measure of sense of agency, that is, the experience of controlling our actions and their consequences. One of the most common measures of temporal binding is the paradigm developed by Haggard, Clark and Kalogeras (2002) based on the Libet clock stimulus. Although widely used, it is not clear how sensitive the temporal binding effect is to the parameters of the clock stimulus. Here, we present five experiments examining the effects of clock speed, number of clock markings and length of the clock hand on binding. Our results show that the magnitude of temporal binding increases with faster clock speeds, whereas clock markings and clock hand length do not significantly influence temporal binding. We discuss the implications of these results.

Public Attitudes to Digital Health Research Repositories: Cross-sectional International Survey.

BACKGROUND: Digital health research repositories propose sharing longitudinal streams of health records and personal sensing data between multiple projects and researchers. Motivated by the prospect of personalizing patient care (precision medicine), these initiatives demand broad public acceptance and large numbers of data contributors, both of which are challenging. OBJECTIVE: This study investigates public attitudes toward possibly contributing to digital health research repositories to identify factors for their acceptance and to inform future developments. METHODS: A cross-sectional online survey was conducted from March 2020 to December 2020. Because of the funded project scope and a multicenter collaboration, study recruitment targeted young adults in Denmark and Brazil, allowing an analysis of the differences between 2 very contrasting national contexts. Through closed-ended questions, the survey examined participants' willingness to share different data types, data access preferences, reasons for concern, and motivations to contribute. The survey also collected information about participants' demographics, level of interest in health topics, previous participation in health research, awareness of examples of existing research data repositories, and current attitudes about digital health research repositories. Data analysis consisted of descriptive frequency measures and statistical inferences (bivariate associations and logistic regressions). RESULTS: The sample comprises 1017 respondents living in Brazil (1017/1600, 63.56%) and 583 in Denmark (583/1600, 36.44%). The demographics do not differ substantially between participants of these countries. The majority is aged between 18 and 27 years (933/1600, 58.31%), is highly educated (992/1600, 62.00%), uses smartphones (1562/1600, 97.63%), and is in good health (1407/1600, 87.94%). The analysis shows a vast majority were very motivated by helping future patients (1366/1600, 85.38%) and researchers (1253/1600, 78.31%), yet very concerned about unethical projects (1219/1600, 76.19%), profit making without consent (1096/1600, 68.50%), and cyberattacks (1055/1600, 65.94%). Participants' willingness to share data is lower when sharing personal sensing data, such as the content of calls and texts (1206/1600, 75.38%), in contrast to more traditional health research information. Only 13.44% (215/1600) find it desirable to grant data access to private companies, and most would like to stay informed about which projects use their data (1334/1600, 83.38%) and control future data access (1181/1600, 73.81%). Findings indicate that favorable attitudes toward digital health research repositories are related to a personal interest in health topics (odds ratio [OR] 1.49, 95% CI 1.10-2.02; P=.01), previous participation in health research studies (OR 1.70, 95% CI 1.24-2.35; P=.001), and awareness of examples of research repositories (OR 2.78, 95% CI 1.83-4.38; P<.001). CONCLUSIONS: This study reveals essential factors for acceptance and willingness to share personal data with digital health research repositories. Implications include the importance of being more transparent about the goals and beneficiaries of research projects using and re-using data from repositories, providing participants with greater autonomy for choosing who gets access to which parts of their data, and raising public awareness of the benefits of data sharing for research. In addition, future developments should engage with and reduce risks for those unwilling to participate.

Barriers to and Facilitators of Technology in Cardiac Rehabilitation and Self-Management: Systematic Qualitative Grounded Theory Review.

BACKGROUND: Dealing with cardiovascular disease is challenging, and people often struggle to follow rehabilitation and self-management programs. Several systematic reviews have explored quantitative evidence on the potential of digital interventions to support cardiac rehabilitation (CR) and self-management. However, although promising, evidence regarding the effectiveness and uptake of existing interventions is mixed. This paper takes a different but complementary approach, focusing on qualitative data related to people's experiences of technology in this space. OBJECTIVE: Through a qualitative approach, this review aims to engage more directly with people's experiences of technology that supports CR and self-management. The primary objective of this paper is to provide answers to the following research question: What are the primary barriers to and facilitators and trends of digital interventions to support CR and self-management? This question is addressed by synthesizing evidence from both medical and computer science literature. Given the strong evidence from the field of human-computer interaction that user-centered and iterative design methods increase the success of digital health interventions, we also assess the degree to which user-centered and iterative methods have been applied in previous work. METHODS: A grounded theory literature review of articles from the following major electronic databases was conducted: ACM Digital Library, PsycINFO, Scopus, and PubMed. Papers published in the last 10 years, 2009 to 2019, were considered, and a systematic search with predefined keywords was conducted. Papers were screened against predefined inclusion and exclusion criteria. Comparative and in-depth analysis of the extracted qualitative data was carried out through 3 levels of iterative coding and concept development. RESULTS: A total of 4282 articles were identified in the initial search. After screening, 61 articles remained, which were both qualitative and quantitative studies and met our inclusion criteria for technology use and health condition. Of the 61 articles, 16 qualitative articles were included in the final analysis. Key factors that acted as barriers and facilitators were background knowledge and in-the-moment understanding, personal responsibility and social connectedness, and the need to support engagement while avoiding overburdening people. Although some studies applied user-centered methods, only 6 involved users throughout the design process. There was limited evidence of studies applying iterative approaches. CONCLUSIONS: The use of technology is acceptable to many people undergoing CR and self-management. Although background knowledge is an important facilitator, technology should also support greater ongoing and in-the-moment understanding. Connectedness is valuable, but to avoid becoming a barrier, technology must also respect and enable individual responsibility. Personalization and gamification can also act as facilitators of engagement, but care must be taken to avoid overburdening people. Further application of user-centered and iterative methods represents a significant opportunity in this space.

Qualitative Synthesis of Young People's Experiences With Technology-Assisted Cognitive Behavioral Therapy: Systematic Review.

BACKGROUND: Cognitive behavioral therapy (CBT) for young people is increasingly being provided using technology-assisted formats. Although there is increasing evidence regarding the efficacy of such approaches, as illustrated by quantitative systematic reviews, the literature has also highlighted challenges with implementation factors, including high attrition rates and variable user engagement. Qualitative review methods can help to address the factors that impact young peoples' experience of technology-assisted cognitive behavioral therapy (tech-assisted CBT) and, thus, enable us to better understand such implementation factors. To date, no such qualitative synthesis exists. OBJECTIVE: The primary aim of this review was to systematically identify and synthesize the qualitative literature concerning the experiences of young people who have used tech-assisted CBT. METHODS: This systematic review applied Thomas and Harden's 2008 qualitative thematic synthesis approach. This involved line-by-line coding of the results sections of included studies and an inductive analysis on identified themes, followed by the generation of analytical themes through a process of iteration and interpretation of the descriptive themes. PsycINFO, ACM Digital Library, PubMed, EMBASE, and JMIR Publications databases were searched. The inclusion criteria were (1) studies involving school-aged young people over preschool age (6 years) but under the age of 18 years, (2) use of any form of tech-assisted CBT for any time period, (3) a stated focus of qualitative data to document the experiences of participants, and (4) studies published in English. The exclusion criteria were (1) interventions only provided face-to-face with no technological component, (2) only focused on the performance of the technology rather than participant experience, and (3) numerical data that sought to represent qualitative data. RESULTS: A total of 14 studies were included in this review. Overall, these studies represented interventions for low mood and anxiety (n=10), trauma or self-harm (n=2), and physical difficulties (n=2). Overall, 5 analytical themes emerged on young people's experiences with tech-assisted CBT: (1) helpfulness, (2) therapeutic process, (3) transferability, (4) gameplay experience, and (5) limitations. In addition, these analytical themes contained the following subthemes: positive experiences, tech-assisted CBT versus face-to-face CBT, understanding of a CBT model, process of change, skills development, application to everyday life settings, parental involvement, character relatedness, playability, negative experiences, and broad content. CONCLUSIONS: Overall, young people's experiences with tech-assisted CBT were mostly positive. The use of gaming environments, relatable characters, concrete metaphors, and age-appropriate narratives contributed to these positive experiences. Evidence suggests that technology can help to mediate face-to-face relationships with therapists and help young people to understand the CBT model. Clear barriers also emerged, including over-reliance on reading and writing skills and dissatisfaction with overly generalized content and comparison with commercial technologies. TRIAL REGISTRATION: International Prospective Register of Systematic Reviews (PROSPERO) CRD42018103388; https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42018103388.

Young People's Online Help-Seeking and Mental Health Difficulties: Systematic Narrative Review.

BACKGROUND: Young people frequently make use of the internet as part of their day-to-day activities, and this has extended to their help-seeking behavior. Offline help-seeking is known to be impeded by a number of barriers including stigma and a preference for self-reliance. Online help-seeking may offer an additional domain where young people can seek help for mental health difficulties without being encumbered by these same barriers. OBJECTIVE: The objective of this systematic literature review was to examine young peoples' online help-seeking behaviors for mental health concerns. It aimed to summarize young peoples' experiences and identify benefits and limitations of online help-seeking for this age group. It also examined the theoretical perspectives that have been applied to understand online help-seeking. METHODS: A systematic review of peer-reviewed research papers from the following major electronic databases was conducted: PsycINFO, Cumulative Index of Nursing and Allied Health Literature, PubMed, Cochrane Library, Association for Computing Machinery Digital Library, and Institute of Electrical and Electronics Engineers Xplore. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed. The search was conducted in August 2017. The narrative synthesis approach to reviews was used to analyze the existing evidence to answer the review questions. RESULTS: Overall, 28 studies were included. The most common method of data collection was through the use of surveys. Study quality was moderate to strong. Text-based query via an internet search engine was the most commonly identified help-seeking approach. Social media, government or charity websites, live chat, instant messaging, and online communities were also used. Key benefits included anonymity and privacy, immediacy, ease of access, inclusivity, the ability to connect with others and share experiences, and a greater sense of control over the help-seeking journey. Online help-seeking has the potential to meet the needs of those with a preference for self-reliance or act as a gateway to further help-seeking. Barriers to help-seeking included a lack of mental health literacy, concerns about privacy and confidentiality, and uncertainty about the trustworthiness of online resources. Until now, there has been limited development and use of theoretical models to guide research on online help-seeking. CONCLUSIONS: Approaches to improving help-seeking by young people should consider the role of the internet and online resources as an adjunct to offline help-seeking. This review identifies opportunities and challenges in this space. It highlights the limited use of theoretical frameworks to help conceptualize online help-seeking. Self-determination theory and the help-seeking model provide promising starting points for the development of online help-seeking theories. This review discusses the use of these theories to conceptualize online help-seeking and identify key motivations and tensions that may arise when young people seek help online.

Altered expression of inflammasomes in Hirschsprung's disease.

AIM OF THE STUDY: The pathogenesis of Hirschsprung's disease-associated enterocolitis (HAEC) is poorly understood. Inflammasomes are a large family of multiprotein complexes that act to mediate host immune responses to microbial infection and have a regulatory or conditioning influence on the composition of the microbiota. Inflammasomes and the apoptosis-associated speck-like protein (ASC) lead to caspase-1 activation. The activated caspase-1 promotes secretion of pro-inflammatory cytokines (IL-1ß and IL-18) from their precursors (pro-IL-1ß and pro-IL-18). Inflammasomes have been implicated in a host of inflammatory disorders. Among the inflammasomes, NLRP3, NLRP12 and NLRC4 are the most widely investigated. Knock-out mice models of inflammasomes NLRP3, NLRP12, NLRC4, caspase-1 and ASC are reported to have higher susceptibility to experimental colitis. The purpose of this study was to investigate the expression of NLRP3, NLRP12, NLRC4, caspase-1, ASC, pro-IL-1ß and pro-IL-18 in the bowel specimens from patients with HSCR and controls. METHODS: Pulled-through colonic specimens were collected from HSCR patients (n = 6) and healthy controls from the proximal colostomy of children with anorectal malformations (n = 6). The gene expression of NLRP3, NLRP12, NLRC4, caspase-1, ASC, pro-IL-1ß and pro-IL-18 was assessed using qPCR. The protein distribution was assessed using immunofluorescence and confocal microscopy. MAIN RESULTS: qRT-PCR analysis revealed that NLRP3, NLRP12, NLRC4, ASC and pro-IL-1ß gene expressions was significantly downregulated in the aganglionic and ganglionic colon of patients with HSCR compared to controls. Confocal microscopy revealed a markedly decreased expression of NLRP3, NLRP12, NLRC4 and ASC protein in the colonic epithelium of aganglionic and ganglionic bowel of patients with HSCR compared to controls. CONCLUSIONS: To our knowledge, this is the first study analyzing NLRP3, NLRP12, NLRC4, ASC and pro-IL-1ß gene expressions in patients with HSCR. Decreased expression of NLRP3, NLRP12, NLRC4, ASC and pro-IL-1ß in the aganglionic and ganglionic bowel may increase susceptibility of HSCR patients to develop HAEC.

Altered expression of caveolin-1 in the colon of patients with Hirschsprung's disease.

BACKGROUND/PURPOSE: The pathogenesis of Hirschsprung's disease-associated enterocolitis (HAEC) is unclear. Caveolin-1 (Cav-1) regulates the functions of different nitric oxide synthase (NOS) isoforms, which play critical roles in inflammation and intestinal epithelial barrier function. We designed this study to investigate the hypothesis that Cav-1 expression is altered in the bowel of patients with Hirschsprung's disease (HSCR). METHODS: HSCR tissue specimens (n = 10) were collected at the time of pull-through surgery and control samples were obtained at the time of colostomy closure in patients with imperforate anus (n = 10). qRT-PCR analysis was undertaken to quantify Cav-1 gene expression, and Western blot analysis was undertaken to determine Cav-1 protein quantification. Immunolabelling of Cav-1 proteins was visualized using confocal microscopy. RESULTS: qRT-PCR and Western blot analysis revealed that Cav-1 was significantly downregulated in the aganglionic and ganglionic colon of patients with HSCR compared to controls (p < 0.01). Confocal microscopy revealed a markedly decreased expression of Cav-1 in colonic epithelium of aganglionic and ganglionic bowel of patients with HSCR compared to controls. CONCLUSION: To our knowledge, this is the first report of significantly decreased Cav-1 expression in patients with HSCR. Decreased expression of Cav-1 in the bowel of HSCR may increase susceptibility to HAEC in HSCR.

Opioid analgesic dose and the risk of misuse, overdose, and death: A narrative review.

PURPOSE: Despite the rise in serious adverse events paralleling increased prescription opioid analgesic use in the United States over the past 2 decades, the association between opioid analgesic dose and the risk of serious adverse health outcomes is incompletely characterized. We sought to synthesize the medical literature for observational studies examining the association between opioid analgesic dose and the risk of serious adverse health outcomes, with particular attention to the outcomes of misuse, abuse, addiction, overdose, and death. METHODS: Searching MEDLINE using PubMed and bibliography review, we identified 22 observational studies published between 2000 and 2015 that assessed the association between opioid analgesic dose and the risk of serious adverse health outcomes. Some of these studies had significant methodological limitations. Twelve reviewed studies examined the outcomes of misuse, overdose, or death; no studies examining the risk of addiction or abuse met our criteria for inclusion. RESULTS: The results of multiple studies clearly indicate an increasing risk of serious adverse health outcomes associated with increasing opioid analgesic dose. In particular, the risk of misuse, overdose, and death increases with increasing opioid analgesic dose. However, there is no opioid dose inflection point beyond which the risk of these adverse health outcomes increases. No opioid analgesic dose is without risk. CONCLUSIONS: The reviewed studies show an increasing risk of serious adverse health outcomes-including misuse, overdose, and death-associated with increasing opioid analgesic dose. Further research is needed to characterize the relationship between opioid analgesic dose and the risk of addiction and abuse. This analysis could inform policy actions for regulators and clinical decision making for providers.

User Experience of Cognitive Behavioral Therapy Apps for Depression: An Analysis of App Functionality and User Reviews.

BACKGROUND: Hundreds of mental health apps are available to the general public. With increasing pressures on health care systems, they offer a potential way for people to support their mental health and well-being. However, although many are highly rated by users, few are evidence-based. Equally, our understanding of what makes apps engaging and valuable to users is limited. OBJECTIVE: The aim of this paper was to analyze functionality and user opinions of mobile apps purporting to support cognitive behavioral therapy for depression and to explore key factors that have an impact on user experience and support engagement. METHODS: We systematically identified apps described as being based on cognitive behavioral therapy for depression. We then conducted 2 studies. In the first, we analyzed the therapeutic functionality of apps. This corroborated existing work on apps' fidelity to cognitive behavioral therapy theory, but we also extended prior work by examining features designed to support user engagement. Engagement features found in cognitive behavioral therapy apps for depression were compared with those found in a larger group of apps that support mental well-being in a more general sense. Our second study involved a more detailed examination of user experience, through a thematic analysis of publicly available user reviews of cognitive behavioral therapy apps for depression. RESULTS: We identified 31 apps that purport to be based on cognitive behavioral therapy for depression. Functionality analysis (study 1) showed that they offered an eclectic mix of features, including many not based on cognitive behavioral therapy practice. Cognitive behavioral therapy apps used less varied engagement features compared with 253 other mental well-being apps. The analysis of 1287 user reviews of cognitive behavioral therapy apps for depression (study 2) showed that apps are used in a wide range of contexts, both replacing and augmenting therapy, and allowing users to play an active role in supporting their mental health and well-being. Users, including health professionals, valued and used apps that incorporated both core cognitive behavioral therapy and non-cognitive behavioral therapy elements, but concerns were also expressed regarding the unsupervised use of apps. Positivity was seen as important to engagement, for example, in the context of automatic thoughts, users expressed a preference to capture not just negative but also positive ones. Privacy, security, and trust were crucial to the user experience. CONCLUSIONS: Cognitive behavioral therapy apps for depression need to improve with respect to incorporating evidence-based cognitive behavioral therapy elements. Equally, a positive user experience is dependent on other design factors, including consideration of varying contexts of use. App designers should be able to clearly identify the therapeutic basis of their apps, but they should also draw on evidence-based strategies to support a positive and engaging user experience. The most effective apps are likely to strike a balance between evidence-based cognitive behavioral therapy strategies and evidence-based design strategies, including the possibility of eclectic therapeutic techniques.

Altered goblet cell function in Hirschsprung's disease.

AIMS AND OBJECTIVES: Hirschsprung's disease-associated enterocolitis (HAEC) is the most serious complication of Hirschsprung's disease (HSCR). HAEC occurs in 17-50% of patients with HSCR and may occur before or after a properly performed pull-through operation. The pathogenesis of HAEC is poorly understood. It is well recognized that a complex mucosal barrier protects, as the first line of defense, the surface of healthy intestinal tract from adhesion and invasion by luminal micro-organisms. Within the intestinal epithelium, goblet cells secrete gel-forming mucins, the major component of mucus, which block the direct attachment of commensal bacteria to the epithelial layer. Mucin 2 (MUC2) is the predominant mucin expressed in humans. Trefoil factor 3 (TFF3) synergizes with mucin and enhances the protective barrier properties of the mucus layer. SAM pointed domain-containing ETS transcription factor (SPDEF) drives terminal differentiation and maturation of secretory progenitors into goblet cells. Krueppel-like factor 4 (KLF4) is a goblet cell-specific differentiation factor in the colon and controls goblet cell differentiation and activates mucin synthesis. We hypothesized that the goblet cell function in the ganglionic pulled-through bowel in HSCR is abnormal and, therefore, we investigated the changes in goblet cell differentiation and functional expression of mucin in the bowel specimens from patients with HSCR. MATERIAL AND METHODS: We investigated MUC2, TFF3, SPDEF and KLF4 expression, and the goblet cell population in the ganglionic and aganglionic bowel of HSCR patients (n = 10) and controls (n = 10) by qPCR, Western blotting, confocal immunofluorescence, and alcian blue staining. RESULTS: The qPCR and Western blotting analysis revealed that TFF3, SPDEF and KLF4 expressions were significantly downregulated in the aganglionic and ganglionic colon of patients with HSCR as compared to controls (p < 0.05). Alcian blue staining revealed that the goblet cell population was significantly decreased in aganglionic and ganglionic colon as compared to controls (p < 0.05). Confocal microscopy revealed a markedly decreased expression of TFF3, SPDEF and KLF4 in colonic epithelium of patients with HSCR as compared to controls. CONCLUSION: This is, to our knowledge, the first report of decreased expression of TFF3, SPDEF, KLF4, and goblet cell population in the colon of patients with HSCR. Altered goblet cell function may result in intestinal barrier dysfunction contributing to the development of HAEC.

Computer-assisted cognitive behavioural therapy: The experiences of adults who have an intellectual disability and anxiety or depression.

BACKGROUND: Despite its evidence base in the general population, computerized cognitive behavioural therapy (cCBT) has not yet been adapted for use with people with intellectual disability. This study aimed to explore the experiences of adults with an intellectual disability who played a cCBT program. METHOD: Twenty-four adults (with a mild or moderate intellectual disability and clinically significant anxiety or depression) who were in the treatment arm of a pilot randomized controlled trial evaluating the cCBT program were individually interviewed. Thematic analysis was used to analyse and report themes within the data. RESULTS: Participants found playing the program to be an enjoyable and novel experience and that it was challenging and helpful. It allowed them to develop and reflect on relationships and increased their awareness of thoughts, feelings and behaviours. CONCLUSIONS: Combining technology with CBT is an effective way to reduce barriers to accessing mental health interventions and technology for this population.

Computerised cognitive-behavioural therapy for adults with intellectual disability: randomised controlled trial.

BackgroundDespite the evidence base for computer-assisted cognitive-behavioural therapy (CBT) in the general population, it has not yet been adapted for use with adults who have an intellectual disability.AimsTo evaluate the utility of a CBT computer game for adults who have an intellectual disability.MethodA 2 × 3 (group × time) randomised controlled trial design was used. Fifty-two adults with mild to moderate intellectual disability and anxiety or depression were randomly allocated to two groups: computerised CBT (cCBT) or psychiatric treatment as usual (TAU), and assessed at pre-treatment, post-treatment and 3-month follow-up. Forty-nine participants were included in the final analysis.ResultsA significant group × time interaction was observed on the primary outcome measure of anxiety (Glasgow Anxiety Scale for people with an Intellectual Disability), favouring cCBT over TAU, but not on the primary outcome measure of depression (Glasgow Depression Scale for people with a Learning Disability). A medium effect size for anxiety symptoms was observed at post-treatment and a large effect size was observed after follow-up. Reliability of Change Indices indicated that the intervention produced clinically significant change in the cCBT group in comparison with TAU.ConclusionsAs the first application of cCBT for adults with intellectual disability, this intervention appears to be a useful treatment option to reduce anxiety symptoms in this population.

Comparing young people's experience of technology-delivered v. face-to-face mindfulness and relaxation: two-armed qualitative focus group study.

BackgroundThe current popularity of mindfulness-based practices has coincided with the increase in access to mobile technology. This has led to many mindfulness apps and programs becoming available, some specifically for children. However, little is known about the experience of engaging with mindfulness through these mediums.AimsTo explore children's experience of mindfulness delivered both face-to-face and through a computer game to highlight any differences or similarities.MethodA two-armed qualitative focus groups design was used to explore children's experiences. The first arm offered mindfulness exercises in a traditional face-to-face setting with guided meditations. The second arm offered mindfulness exercises through a computer game avatar.ResultsThemes of relaxation, engagement, awareness, thinking, practice and directing attention emerged from both arms of focus groups. Subthematic codes highlight key differences as well as similarities in the experience of mindfulness.ConclusionsThese results indicate that mindfulness delivered via technology can offer a rich experience.

Increased population of immature enteric glial cells in the resected proximal ganglionic bowel of Hirschsprung's disease patients.

BACKGROUND: Enteric glial cells are essential for normal gastrointestinal function. Abnormalities in glial structure, development, or function lead to disturbances in gastrointestinal physiology. Fatty acid-binding protein 7 (FABP7) is a marker of immature enteric glial cells, whereas S100 is expressed only by mature glial cells. Patients with Hirschsprung's disease (HSCR) often suffer from dysmotility and enterocolitis despite proper surgery. We designed this study to determine the distribution and expression of glial cells in patients with HSCR compared to normal controls. METHODS: We investigated FABP7, S100, and PGP 9.5 expressions in both the ganglionic and aganglionic bowel of patients with HSCR (n = 6) versus normal control colon (n = 6). Protein distribution was assessed by using immunofluorescence and confocal microscopy. Gene and protein expressions were quantified using quantitative real-time polymerase chain reaction (qPCR), Western blot analysis, and densitometry. RESULTS: qPCR and Western blot analysis demonstrated a significantly increased FABP7 expression in ganglionic specimens compared to control specimen (P < 0.05). Confocal microscopy revealed FABP7+ glia cells lie under the colonic epithelium and in close apposition to enteric neurons in the ganglionic bowel. CONCLUSIONS: The significantly increased number of immature enteric glial cells (EGCs) in the ganglionic bowel of HSCR patients may have adverse effect on the function of enteric neurons and intestinal barrier and thus predispose these patients to intestinal motility problems and enterocolitis.

Rationale and design of BISTRO: a randomized controlled trial to determine whether bioimpedance spectroscopy-guided fluid management maintains residual kidney function in incident haemodialysis patients.

BACKGROUND: Preserved residual kidney function (RKF) and normal fluid status are associated with better patient outcomes in incident haemodialysis patients. The objective of this trial is to determine whether using bioimpedance technology in prescribing the optimal post-dialysis weight can reduce the rate of decline of RKF and potentially improve patient outcomes. METHODS/DESIGN: 516 pateints commencing haemodialysis, aged >18 with RKF of > 3 ml/min/1.73 m2 or a urine volume >500 ml per day or per the shorter inter-dialytic period will be consented and enrolled into a pragmatic, open-label, randomized controlled trial. The intervention is incorporation of bioimpedance spectroscopy (BI) determination of normally hydrated weight to set a post-dialysis target weight that limits volume depletion, compared to current standard practice. Clinicians and participants will be blinded to BI measures in the control group and a standardized record capturing management of fluid status will be used in all participants. Primary outcome is preservation of residual kidney function assessed as time to anuria (≤100 ml/day or ≤200 ml urine volume in the short inter-dialytic period). A sample size of 516 was based upon a cumulative incidence of 30% anuria in the control group and 20% in the treatment group and 11% competing risks (death, transplantation) over 10 months, with up to 2 years follow-up. Secondary outcomes include rate of decline in small solute clearance, significant adverse events, hospitalization, loss of vascular access, cardiovascular events and interventions, dialysis efficacy and safety, dialysis-related symptoms and quality of life. Economic evaluation will be carried out to determine the cost-effectiveness of the intervention. Analyses will be adjusted for patient characteristics and dialysis unit practice patterns relevant to fluid management. DISCUSSION: This trial will establish the added value of undertaking BI measures to support clinical management of fluid status and establish the relationship between fluid status and preservation of residual kidney function in incident haemodialysis patients. TRIAL REGISTRATION: ISCCTN Number: 11342007 , completed 26/04/2016; NIHR Portfolio number: CPMS31766; Sponsor: Keele University.

Attrition from Web-Based Cognitive Testing: A Repeated Measures Comparison of Gamification Techniques.

BACKGROUND: The prospect of assessing cognition longitudinally and remotely is attractive to researchers, health practitioners, and pharmaceutical companies alike. However, such repeated testing regimes place a considerable burden on participants, and with cognitive tasks typically being regarded as effortful and unengaging, these studies may experience high levels of participant attrition. One potential solution is to gamify these tasks to make them more engaging: increasing participant willingness to take part and reducing attrition. However, such an approach must balance task validity with the introduction of entertaining gamelike elements. OBJECTIVE: This study aims to investigate the effects of gamelike features on participant attrition using a between-subjects, longitudinal Web-based testing study. METHODS: We used three variants of a common cognitive task, the Stop Signal Task (SST), with a single gamelike feature in each: one variant where points were rewarded for performing optimally; another where the task was given a graphical theme; and a third variant, which was a standard SST and served as a control condition. Participants completed four compulsory test sessions over 4 consecutive days before entering a 6-day voluntary testing period where they faced a daily decision to either drop out or continue taking part. Participants were paid for each session they completed. RESULTS: A total of 482 participants signed up to take part in the study, with 265 completing the requisite four consecutive test sessions. No evidence of an effect of gamification on attrition was observed. A log-rank test showed no evidence of a difference in dropout rates between task variants (χ22=3.0, P=.22), and a one-way analysis of variance of the mean number of sessions completed per participant in each variant also showed no evidence of a difference (F2,262=1.534, P=.21, partial η2=0.012). CONCLUSIONS: Our findings raise doubts about the ability of gamification to reduce attrition from longitudinal cognitive testing studies.